Even as the bar category gets a piece of the keto action, focusing on health and wellness long-term will ensure brands have staying power

Raising the Bar with Keto

The best bone health nutrients give women the foundation to age healthily

Strong Women

Longevity by Nature (Temecula, CA) has recently entered into two strategic marketing and distribution partnerships with National Sales Associates LLC, a national sales and marketing brokerage, and United Natural Foods Inc., North America’s premier food wholesaler. As part of the agreements, National Sales Associates will market Longevity by Nature products throughout its national sales network of more than 160 associates. United Natural Foods, for its part, as a wholesale distributor of natural, organic, and specialty foods and non-food products will explore potential placements for Longevity by Nature products.

“These strategic partnerships will help drive future sales by significantly enhancing our ability to reach retailers and consumers interested in our unique natural wellness solutions,” said Abdul Alkayali, Longevity by Nature vice president and cofounder, in a press release. “Both National Sales Associates and United Natural Foods have tremendous presence, resources and expertise in the natural products marketplace.”

Longevity by Nature’s ingredient portfolio includes KollaJell, the only patented, edible wild caught jellyfish collagen peptides that support cognitive function, Telos95, a blend of natural polyphenols isolated from proprietary grapevine and organic olive leaves that support healthy aging, and Persimonal, a botanical extract of persimmon leaves rich in flavonoids, polyphenols, tannins, and organic acids that support cardiovascular health and immunity.

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Longevity by Nature has recently entered into two strategic marketing and distribution partnerships with National Sales Associates LLC and United Natural Foods Inc.

Longevity by Nature announces new marketing and distribution partnerships

The high-fat, low-carb diet known as the ketogenic (“keto”) diet continues gaining fans in the food space. According to Mintel’s Global New Products Database, foods and beverages launched with keto claims accounted for 2.3% of all food and beverage launches between June 2020 and May 2021, compared to just 1.3% of all launches during that same time frame the previous year.

 Consumers are seeking keto alternatives to their favorite foods because the ketogenic diet promises weight-loss benefits—and, let’s face it, people will always want to lose weight. While low-carb is not a particularly new concept (remember the Atkins diet?), new variations of the ketogenic diet, such as the Whole30 diet, have cropped up and renewed interest. In some ways, too, the Paleo diet has keto qualities. With any diet, convenient on-the-go solutions are an attractive proposition; therefore, it’s no surprise that keto is advancing in the bar space.

According to SPINS, during the 52 weeks ending May 15, 2021, products tapping into the keto trend—specifically, shelf-stable cookies and snack bars with a low-to-no net-carb content—saw 21.31% growth in sales compared to the previous year.

It’s clear that consumers are interested in keto products, and manufacturers want to get a piece of that action, which is not always easy from a formulation standpoint. For example, That’s It (Los Angeles), a bar brand that makes products predominantly from fruit, saw the keto category as a major opportunity but also a major challenge. You see, the keto diet limits the number and types of fruit one can eat due to many fruits’ prohibitive carbohydrate content. After much hard work, That’s It achieved a bar that is not only keto certified but one that also had a great deal of added value.

“We’ve been monitoring the keto space for a while,” explains Lior Lewensztain, founder and CEO of That’s It. “We were looking to try some new innovations, being very data focused, and came across this convergence of keto and coffee energy in our data as trends that were obviously ticking up,” he tells 

 “We were very pleased that we were able to create a plant-based keto product, as well as one of the cleanest keto products you’ll find, at only six ingredients. If you look at any of these keto bars out there, they just have a really long list of ingredients. We were able to keep it super clean, super premium, and still able to integrate this coffee energy aspect.”

The product, called Keto Kick, contains only six ingredients. In addition to dates and tapioca fiber, there’s organic garbanzo beans, organic cocoa, sea salt, and organic, single-source Ethiopian coffee delivering 95 mg of caffeine or one cup of coffee worth of caffeine.

For keto bar makers, one lesson to learn from this example is that a convergence of attributes will attract a wider range of consumers. Keto is big, indeed, but so is energy. On the other hand, consumers also love clean-label products with small ingredient decks.

The bar category certainly took a hit during the pandemic because of the lack of movement necessitating on-the-go products, but as the country begins to recover from the pandemic, it’s important to observe what strategies resulted in the best outcomes. In Lewensztain’s view, it was his brand’s focus on health and wellness that allowed it to thrive, even during the pandemic. A focus on health and wellness can mean healthy, clean ingredients as well as functional benefits.

“I think that’s where consumers went during the pandemic, so we were fortunate in that we weren’t just a snack bar or a junk food–type item,” says Lewensztain. “With the focus on health and wellness, consumers more so than ever really started paying attention to eating in a way that allows them to maintain their health and hopefully feel better, so we were perfectly aligned with that.”

Keto, a Long-Lasting Trend? New Keto Product Launches Double in Past Year.

” Food Navigator-USA.com. Published online June 28, 2021.

From fad to forever: One brand explains how keto companies must look beyond the diet alone to offer more of what consumers want.

Raising the Bar with Keto: Even as the bar category gets a piece of the keto action, focusing on health and wellness long-term will ensure brands have staying power

 compared a novel oral liquid iron-containing food supplement called >Your< Iron Syrup to commonly prescribed iron sulphate. In the study, mice were fed a low-iron diet for 11 weeks to induce a significant decrease in blood hemoglobin and hematocrit, then supplement with either the liquid iron supplement or iron sulphate for two weeks.

Results showed that supplementation with >Your< Iron Syrup significantly improved several markers of iron deficiency, including serum iron concentration, transferrin saturation, and ferritin levels in both male and female mice. Iron sulfate induced a similar response, but did not significantly improve serum iron and serum ferritin in both sexes. However, iron sulphate did significantly increase liver-iron content, while the liquid iron supplement did not.

Iron sulphate is a common preparation to treat iron deficiency, but is associated with poor tolerability. >Your< Iron Syrup, a proprietary formulation containing 14 mg of elemental iron in the form of branded micronised microencapsulated ferric iron, 0.7 mg of vitamin B6, and 1.25 g of vitamin B12 as active ingredients per 5 mL of the product, touts better tolerability and a high level of effectiveness.

Pirman T et al. “Supplementation with >Your< Iron Syrup corrects iron status in a mouse model of diet-induced iron deficiency.” 

A recent animal study compared a novel oral liquid iron-containing food supplement called >Your< Iron Syrup to commonly prescribed iron sulphate. 

Novel liquid iron supplement significantly improved iron content in animal study

Alissa Marrapodi is Industry Insights Contributor, Custom Content Editor, MJH Life Sciences.

NSF International (Ann Arbor, MI) created an introductory “GMPs for Dietary Supplements – 21 CFR 111 Overview” eLearning module, and with the promo code “DSHEA27” (from Oct 25 – 31, 2021), participants can access it at no cost. 

The module, usually $499, offers a historical review of regulations in the dietary supplement industry, their evolution, and subparts of 21 CFR 111. Upon successful completion of the course, participants will receive NSF’s Dietary Supplements certificate.

“DSHEA was landmark legislation in 1994 and it’s important for anyone in the dietary supplements industry to understand it,” said Casey Coy, senior manager, training, and consulting at NSF International, in a press release. “To complement our virtual, instructor-led and in-person training options, we’ve launched an entire suite of self-paced, eLearning courses on DSHEA and the regulation it created, 21 CFR 111 GMP, and we hope this open-access promotion will encourage professional development in our industry.”

These dietary supplement GMP courses are also available the week of Oct. 25:

GMPs for Dietary Supplements – 21 CFR 111 GMP Overview and Subparts A, P, H, and I (1 module)

GMPs for Dietary Supplements – 21 CFR 111 Subparts B, C and D (1 module)

GMPs for Dietary Supplements – 21 CFR 111 Subparts E, K, F and J (1 module)

GMPs for Dietary Supplements – 21 CFR 111 Subparts G, L, M, N, O and Compliance (1 module)

GMPs for Dietary Supplements – 21 CFR 111 Comprehensive Overview (4 modules + final assessment)

NSF International created an introductory “GMPs for Dietary Supplements – 21 CFR 111 Overview” eLearning module, and with the promo code “DSHEA27” (from Oct 25 – 31, 2021), participants can access it at no cost.

NSF International offers open access to GMP eLearning

Osvaldo Marinotti, PhD, senior biochemist for CV Sciences

 welcomes Osvaldo Marinotti, PhD, senior biochemist for CV Sciences (San Diego, CA), to its

 (EAB). Marinotti earned his PhD in biochemistry from the University of Sao Paulo in Brazil, where he also earned his MSc in biochemistry and BSc in biology. He has over 30 years of research experience as well as an extensive record of scientific publications and international collaborations. In addition to his position at CV Sciences, Marinotti founded and leads research at MTEKPrime, a research consultancy specializing in biotechnology, genetic engineering, molecular biology, and biochemistry.

, ND, represented CV Sciences on the EAB as its senior vice president of scientific and regulatory affairs. MacKay will continue to be an EAB member, representing the Consumer Healthcare Products Association (CHPA; Washington, D.C.) as its senior vice president of dietary supplements.

For a full list of Nutritional Outlook’s Editorial Advisory Board members, click 

Marinotti has over 30 years of research experience as well as an extensive record of scientific publications and international collaborations.

Nutritional Outlook welcomes Osvaldo Marinotti, PhD, senior biochemist for CV Sciences, to editorial advisory board

Photo © Vectorfusionart - Stock.adobe.com

The market for bone health dietary supplements is strengthening in response to growing consumer concerns about aging. One recent report by Mordor Intelligence predicts the bone health market will increase at a 6.3% CAGR through 2026.

Postmenopausal and aging women are among the highest at-risk groups likely to experience bone loss and therefore represent a key target in the bone health supplements market.

 As the population ages and more women begin prioritizing their bone health, scientifically validated bone health formulations will gain their attention. Supplement marketers and nutrition researchers are learning more about the many ways nutrients can support aging bones—and advancing their products accordingly.

One recent discovery has opened up new opportunities in bone health—for gut health ingredients, that is. In fact, new studies have found that the gut microbiota can influence bone health, says Titti Niskanen, PhD, director of R&D and clinical operations for probiotics supplier Probi (Lund, Sweden). This discovery has led to the emergence of a new field of research: osteomicrobiology.

“Although the exact mechanism explaining the bacterial role in this health area is not clearly elucidated, there are various pathways suggested for how probiotics and gut bacteria may affect bone homeostasis and bone metabolism,” Niskanen says. “The overall hypothesis involves the activation or downregulation of osteoclasts, the cells that are responsible for bone resorption. Probiotics are believed to reduce the activation of cells involved in the inflammatory response that leads to activation of the osteoclasts.”

One randomized, double-blind, placebo-controlled, multicenter trial

 funded by Probi examined the efficacy of probiotics on lumbar spine bone mineral density in 232 postmenopausal women aged 45 to 70. The subjects were randomly assigned to receive either Probi’s branded Osteo product, which is a probiotic supplement containing a 10 billion–colony-forming unit (CFU) combination of 

 15313 (n = 116), or a placebo (n = 116), once daily for 12 months. The subjects were assessed for lumbar spine bone mineral density at baseline and at the study’s conclusion.

The control group exhibited an average bone loss of 0.72% over the course of the study. The Probi group experienced 0.01% bone loss. The researchers concluded that this mix of three 

strains may help prevent bone loss in postmenopausal women.

Niskanen, who was one of the authors of this study, says Probi is now working on a new trial to investigate the effects of Probi Osteo on bone metabolism, microarchitecture, and density. Probi is also developing more product formats for Osteo and has already launched a powder and a shot formulation.

Are vegans at higher risk of bone fractures than omnivores? That’s the question posed by a recent cross-sectional observational pilot study

The subjects had been following either a vegan diet (n = 36) or an omnivorous diet (n = 36) for at least one year and were assessed for bone mineral density via calcaneal quantitative ultrasound, plus blood and urine concentrations of nutrients like calcium and vitamin K1.

The vegan group had lower levels of calcium, lysine, zinc, and vitamins A and B2, while the omnivore group had lower levels of vitamin K1, folate, and glutamine.Kriti Chaudhary, head of business development for Vedic Lifesciences (Mumbai, India), says this pilot study warrants further research on whether veganism affects bone health.

Legacy ingredients like calcium, magnesium, and vitamin D still dominate bone health shelves, but newer ingredients are creating market disruption. Michael A. Smith, MD, director of education for supplements company Life Extension (Ford Lauderdale, FL), says emerging consumer awareness around vitamin K2 is opening up opportunities for synergistic bone health blends.

“While vitamin K2 may not be new to bone health, this ingredient is still emerging for the general consumer,” Smith says. “Vitamin K2 has been shown to be essential for bone mineralization because it’s a cofactor for the carboxylation of osteocalcin. Clinical studies have shown that when you combine vitamin K with vitamin D3 and calcium, there’s a significant increase in bone mass density.”

One 2014 literature review of 11 randomized clinical trials

 examined the effects of menatetrenone, a synthetic ingredient that is bioidentical to menaquinone-4 (a form of vitamin K2), on bone mineral density, incidence of bone fracture, and serum undercarboxylated osteocalcin concentrations in postmenopausal women with osteoporosis. Seven of the trials assessed the effects of menatetrenone on bone mineral density, and four assessed the effects of menatetrenone on incidence of vertebral fracture. While the review author cautions that the trials had small sample sizes, the review concluded that menatetrenone decreases serum concentrations of undercarboxylated osteocalcin, increases lumbar spine bone mineral density, and reduces the incidence of fractures in postmenopausal women with osteopenia or osteoporosis.

In December 2020, Life Extension launched Bone Restore Elite with Super Potent K2, a blend of menaquinone-4, calcium, vitamin D3, and trace minerals, including magnesium, zinc, manganese, boron, and silicon. “While calcium still holds the largest ingredient market share for bone health, ingredients like vitamin D and magnesium are expected to see modest market growth through 2024,” Smith notes. “The benefits of vitamin K2 are becoming more well known for bone health, so I think we will start to see more products with vitamin K2 combined with traditional bone health ingredients.”

Bone health products are expanding to newer formats, says Smith. Capsules are still the main delivery system, but products like gummies and ready-to-drink (RTD) beverages are also hitting the bone health market.

In July 2020, Evolva (Reinach, Switzerland) announced the second in a series of publications from the Resveratrol Supporting Healthy Aging in Women (RESHAW) clinical study.

 This randomized, double-blind, placebo-controlled crossover trial assessed the effects of two 75-mg capsules per day of Evolva’s Veri-te brand of resveratrol (n = 63) versus placebo (n = 65) on cognitive and cerebrovascular function, bone health, and cardiometabolic health in postmenopausal women over the course of two years.

The study, which received supplementary funding from Evolva, found that resveratrol consumption increased bone mineral density, decreased plasma C-telopeptide (CTx) in CTx testing, and reduced the 10-year probability of major osteoporotic fractures, including hip fractures. Resveratrol was found to act synergistically with vitamin D and calcium to protect bone health.

Vitamin K2 Provides Dual-Action Calcium Regulation

Trygve Bergeland, PhD, vice president of science for Kappa Bioscience AS (Oslo, Norway), says that within the next two years, the number of dietary supplement consumers actively seeking out vitamin K2 will double from 8% to 16%. The COVID-19 pandemic could inspire further growing demand for bone health supplements driven by increased interest in immune health products, Bergeland says.

“Brands increasingly understand via the immune health product development process the value of a combination of vitamins D3 and K2 for the multiple applications of D3,” Bergeland says. “Of course, the focus here is on immune health, but consequently, we expect a renaissance of vitamin K2 for bone health over the next two years.”

Vitamin K2 works synergistically with vitamin D to both improve bone health and also to reduce cardiovascular risks, Bergeland explains. Vitamin D increases calcium absorption, and vitamin K2 ensures calcium will be incorporated into the bone matrix rather than remaining in the bloodstream. While studies have shown supplementation with either vitamin D or vitamin K2 will limit bone loss in postmenopausal women, pairing the two vitamins together will go beyond limiting bone loss to increase bone mineral density, Bergeland says. “Vitamin K2 is a necessary cofactor for activation of matrix Gla protein (MGP), a calcium-binding protein. When activated, MGP binds excess calcium in the blood and prevents it from being deposited in arteries. Vitamin K2 ensures calcium will reach the bones.”

Vitamin K2’s second mechanism of action involves activating osteocalcin. Fully activated osteocalcin will bind to free-floating calcium in the blood and transport it to the bone matrix, ensuring the maximum amount of free calcium is devoted to building bones, Bergeland says. In fact, in May 2020, Kappa Bioscience launched a new educational program explaining the synergistic relationship between vitamins D3 and K2.

In 2020, the Canadian Space Agency (Saint-Hubert, Canada) and the University of Calgary (Calgary, Canada) concluded a five-year study

 on the effects of outer space travel on bone health. The TBone study observed 17 astronauts who underwent wrist and ankle imaging before and after their mission. The astronauts supplied blood and urine samples throughout the mission and provided information regarding their diet and exercise regimen as well as their supplements and medications. The study found that astronauts experience 20 years’ worth of bone loss during a six-month space mission.

Companies like SpaceX, Blue Origin, and Space Adventures have either already sent private citizens into space or will do so before the end of 2021. While the spacefaring market for bone health supplements is a very small one, the need nonetheless exists. Could this be an interesting novelty market, or an opportunity for a committed bone health brand to partner with a space agency and run a “Good Enough for Astronauts” influencer campaign?

Postmenopausal women may be the primary buyer of bone health supplements, but ongoing research is demonstrating that younger women in their 30s and 40s can also benefit from bone health ingredients.

A recent randomized, double-blind, placebo-controlled clinical trial

 investigated the effects of a protein powder fortified with bone health ingredients on carboxylated and undercarboxylated osteocalcin, bone alkaline phosphatase, urinary calcium-to-creatine ratio, and other biomarkers of bone health in healthy Indian women between the ages of 25 and 45. The subjects were randomly assigned to receive either two 30-g servings of a high-protein nutritional powder dissolved in 200 ml of water (n=52), or a placebo (n=50), daily for six months. The two 30-g servings of nutritional powder combined contained 400 IU of vitamin D2, 9 g of protein, 55 mcg of vitamin K2, 600 mg of calcium, and a variety of other nutrients. The placebo was a low-protein drink powder with 47 g of carbohydrates, 10.8 g of sugar, 3 g of protein, and no vitamins or minerals per daily serving.

After six months, the test group exhibited a 53% increase in carboxylated and undercarboxylated osteocalcin (c-OC/uc-OC) and a 33% decrease in serum C-telopeptide CTx (s-CTX-1). The control group’s mean c-OC/uc-OC concentration increased by 45% from baseline, and s-CTX-1 decreased 23% from baseline. The between-group difference in osteocalcin ratios was found to be statistically significant (p < 0.05) after three months, but not after six months.

Kriti Chaudhary, head of business development for contract research organization Vedic Lifesciences (Mumbai, India), says this trial shows that micronutrient-fortified drinks hold promise for improved bone health among young women.

“Young Indian women may be at risk of poor bone health due to malnutrition,” Chaudhary says. “This trial showed favorable changes in bone turnover markers and calcium homeostasis. Such changes in older adults have been associated with slower bone loss and reduced fracture risk.”

Bone health ingredients are expected to thrive as aging, health-conscious consumers look for ways to reduce fracture risk and maintain bone density. With more choices than ever, consumers could move farther away from calcium-only products and seek out more complex formulas in diverse formats. The next opportunities in bone health will be for innovative blends that come in convenient formats like gummies or RTD beverages.

Bone and Joint Health Ingredients Market – Growth, Trends, COVID-19 Impact, and Forecasts (2021-2026

National Osteoporosis Foundation website. “

Probiotic treatment using a mix of three Lactobacillus strains for lumbar spine bone loss in postmenopausal women: A randomised, double-blind, placebo-controlled, multicentre trial

 vol. 1, no. 3 (November 1, 2019): E154-E162

Vitamin K2 therapy for postmenopausal osteoporosis

Randomised controlled trial of nutritional supplement on bone turnover markers in Indian premenopausal women

Vegan diet and bone health – Results from the cross-sectional RBVD study

Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: A randomized, placebo-controlled trial

vol. 35, no. 11 (November 2020): 2121-2131

Women are finding many approaches to support aging bones as supplement formulas grow increasingly sophisticated and diverse.

Strong Women: The best bone health nutrients give women the foundation to age healthily

Artemis International (Fort Wayne, IN) has signed a distribution agreement for the U.S. with Distillerie Bonollo Umberto S.p.A, a leader in the distillation of grappa. As part of the agreement, Artemis will be representing Bonollo’s Ecovitis, a standardized grape seed extract with the highest level of oligomeric proanthocyanidins (OPC) available. Ecovitis employs a proprietary and innovative water-based membrane extraction method.

“We are always looking to diversify our ingredient portfolio with innovative, science-supported products,” said Leslie Gallo, president of Artemis International, in a press release. “Our focus has been on dark berry extracts – elderberry, aronia berry, tart cherry, etc., so we are excited about this new venture with Bonollo, and adding Ecovitis grape seed extract to our offerings."

“The strategic agreement with Artemis International is instrumental for Bonollo,” stated Paolo Morazzoni, scientific advisor of Distillerie Bonollo Umberto. “We are excited to introduce to the North American market our advanced technological approach for introducing new generations of plant-derived extracts such as Ecovitis.”

Learn more at SupplySide West 2021, where Artemis International (Booth #2757) will discuss the ingredient in more detail.

Artemis International has signed a distribution agreement for the U.S. with Distillerie Bonollo Umberto S.p.A, representing Bonollo’s Ecovitis, a standardized grape seed extract. 

Artemis International announces new distribution agreement for novel grape seed extract

Armada Nutrition (Springhill, TN) is broadening its operation capacity with a new 438,000-square-foot nutraceutical facility in Utah. It will be, together with Armada’s Tennessee facility, be part of over 750,000 square feet of manufacturing space and will be fully operational in Q2 2022. It will have BRC, NSF, NSF for Sport, and ISO 17025 certifications. 

“Our approach with Armada has been to offer the speed, service, and innovation that the industry demands while delivering the quality and safety standard you would expect from a publicly-traded company,” said Armada president Brent Laffey, in a press release.

Further driving Armada’s growth is vertical integration afforded by sister company Prinova. The combined purchasing power of both Nagase Group entities far surpasses any competitors in the nutraceutical contract manufacturing space.

“We’re extremely excited about the Utah facility expansion, and the plans to bring more high-end contract manufacturing capacity to the industry and to our customers,” said Prinova president and CEO Don Thorp, in a press release. “Now more than ever our customers are interested in reliability, safety, and quality in their supply chain, and this new facility will allow us to continue to deliver on that expectation.”

Armada Nutrition is broadening its operation capacity with a new 438,000-square-foot nutraceutical facility in Utah.

Armada Nutrition to open new nutraceutical facility in Utah

The joint health ingredients market is seeing a flurry of new activity as demand for a new generation of products leads formulators to eschew legacy ingredients like glucosamine and chondroitin in favor of emerging ingredients like collagen and turmeric. To gain validation, these next-generation joint health ingredients are focusing on robust clinical trials and formulation.

Collagen supplements recently made the leap from the beauty aisle to the joint health aisle based on studies showing it may relieve joint pain. Research on the interactions between the various types of collagen is now opening up new opportunities for synergistic, combination joint health supplements blending complementary ingredients in a single product.

 examined the effects of Fortigel, a branded bioactive collagen peptide by Gelita (Eberbach, Germany), on knee pain in 180 physically active adults aged 18 to 30 with activity-related joint pain and scores above 20 on the Visual Analog Scale (VAS) for pain. The subjects were given the McMurray test for meniscus injury, the Steinmann I and II tests, and the Butler drawer test to assess ligament stability at baseline and on study conclusion. Subjects received either 5 g of Fortigel (n = 98), or a placebo (n =82), daily for 12 weeks. After 12 weeks, the group receiving collagen peptides experienced an improvement in activity-related joint pain as assessed on the VAS, by the physician, and through self-report. The study authors concluded collagen peptides can reduce knee pain during activity.

Angie Rimel, marketing communications manager for Gelita, says collagen is becoming popular in multi-ingredient products especially. “Collagen is very easy to formulate with,” Rimel says. “There’s a growing trend of blend products, like protein blends or with vitamins or prebiotics.”

Abdul Alkayali, vice president of Certified Nutraceuticals Inc. (Temecula, CA), says some of the most exciting innovation in collagen has to do with a new source: jellyfish. In fact, Alkayali expects invertebrates to replace mammals as the primary source of collagen in the coming years.

“Jellyfish collagen supplies the body with multiple types of collagen peptides and essential minerals that are only found in edible jellyfish collagen,” Alkayali says. “New research on jellyfish has increased tremendously.”

A 2017 60-day prospective single-center observational study

 assessed Certified Nutraceuticals’ branded TendoGuard, a joint health blend including Types I, II, V, and X collagen, as well as hyaluronic acid, chondroitin sulfate, and mucopolysaccharides. This study examined the effects of a 750 mg/day dose of TendoGuard on joint pain and range of motion in 20 men and women aged 45 to 75 with a history of a knee disorder. Subjects were assessed for range of motion via goniometer, pain via the Borg scale, and muscle strength via a sphygmomanometer. After 60 days, the subjects saw improvements in range of motion, pain, and muscle strength. While this study lacked a control group, the study authors concluded that TendoGuard reduced symptoms of joint discomfort.

Studies like these are driving sales of collagen products in the joint health market. Douglas Jones, global sales and marketing manager for Biocell Technology LLC (Irvine, CA), says consumers are looking for clinically validated ingredients that provide noticeable benefits. He expects the joint health market to present opportunities for collagen brands that have clinical research behind them.

“Biocell has seen our collagen sales increase with some customers by over 100% within the last 18 months,” Jones says. “We see consumers looking for at-home solutions to maintain their joint health. The future in joint health is very bright. Millennials are now in their 30s, and this population is very focused on supply-side transparency and branded ingredients with clinical evidence.”

While Millennials represent a growing opportunity for future growth, most joint health consumers are still older adults. A 2021 consumer survey by Lonza (Basel, Switzerland) found that the average joint health consumer is between the ages of 45 and 64. According to Lonza’s research, joint health supplement consumers tend to be well educated and have high incomes. Lindsey Toth, RD, associate director of health ingredients for Lonza, says that with one in six people projected to be 65 years old or older by 2050, now is the time to begin laying the groundwork of consumer education campaigns.

“While collagen has taken center stage in recent years, there is largely little known by consumers about the different types of collagens and the difference in benefits they confer,” Toth says. “Lonza has invested significant research in understanding the benefits of undenatured type II collagen.”

Lonza’s branded UC-II collagen, an undenatured type II collagen ingredient, has been found to increase mobility and reduce joint discomfort in clinical studies, Toth says. One of the advantages of this type of collagen, Toth notes, is convenience of delivery. “UC-II collagen can be taken in a tiny, once-daily, easy-to-swallow dose. Pill fatigue and swallowability concerns are a huge barrier for most aging consumers.”

While collagen is an effective ingredient for joint health, not all types of collagen are created equal. Jaume Reguant, healthcare director for Bioiberica (Barcelona, Spain), says formulators who want to work with collagen will need to consider which type of collagen is best for their application.

“Native type II collagen is an effective joint health ingredient and compared to its hydrolyzed counterpart requires a much lower dosage,” Reguant says. “This means it can be incorporated alongside other beneficial ingredients to support joint health.”

“Emerging ingredients like this are facilitating a new era of mobility health that appeals to a wider range of people who see movement as a fundamental part of their physical and mental well-being,” he adds.

 examined the efficacy of combining Bioiberica’s branded Collavant n2 ingredient (formerly called 2Cool), which is an undenatured type II collagen, and Mobilee, which is a hyaluronic acid matrix ingredient, in a formula that also included Bioiberica’s chondroitin sulfate and glucosamine hydrochloride ingredients. The study assessed the blend’s effects on articular cartilage, synovial membrane, and subchondral bone in 54 rabbits with induced osteoarthritis. The rabbits were randomly assigned to receive a daily dose of either 1) chondroitin sulfate (CS) plus glucosamine hydrochloride (GH) and hyaluronic acid (HA) (n=18), 2) CS plus GH and HA with added Collavant n2 (n=18), or 3) nothing (n=18). Each group was divided into three subgroups (n=6) that were sacrificed after 28, 56, or 84 days. After sacrifice, the rabbits were dissected and evaluated. The rabbits that received the combination of CS, GH, and HA showed milder degenerative changes relative to the control group. The addition of Collavant strengthened this protective effect, the researchers concluded.

Other new research on collagen is demonstrating the viability of a personalized nutrition approach. Liz Clarke, CFS, technical marketing manager for Nitta Gelatin (Morrisville, NC), says new research on joint health ingredients goes beyond providing scientific substantiation of health benefits for the general population. Instead, studies are now zeroing in on clinical personalization for specific demographics like younger athletes or seniors with mobility issues.

One recent randomized, double-blind, placebo-controlled clinical trial

 on Nitta Gelatin’s branded Wellnex Replenwell collagen peptide examined the effects of collagen supplementation on joint pain in healthy male university students aged 18 to 21 who were members of the Josai University running club in Sakado, Japan. The students were randomly assigned to receive either 5 g of Replenwell per day (n = 25) or a maltodextrin placebo (n = 21), for eight weeks. After four weeks, the placebo group saw an increase in levels of interleukin-6 (IL-6), a biomarker of inflammation. The collagen peptide group did not see any significant changes in IL-6 levels. The study found that a daily dose of Replenwell taken for four weeks reduced joint discomfort.

“Personalization is the key here,” Clarke says. “We’re seeing significant results with lower dosage rates for active, younger participants than we have in previous studies looking at the effects on older populations with preexisting joint conditions. While it’s common-sense that different populations would have differing needs, being able to quantify that into dosage requirements is new for collagen.”

One relative newcomer to the joint health market is starting to shake things up and threaten the dominance of legacy ingredients. Recent research is showing that turmeric

can reduce joint inflammation in more ways than one.

Eric Anderson, managing director of NXT USA (Metuchen, NJ), says the company’s branded TamaFlex, a patent-pending blend of 

 seed and turmeric rhizome extracts, is proving to be effective in addressing joint health issues like comfort, flexibility, and function. One 2019 randomized, double-blind, placebo-controlled study

 examined the effects of TamaFlex in 90 non-arthritic subjects with knee pain and joint discomfort. Subjects were randomized to receive either 250 mg (n=30) or 400 mg (n=30) of TamaFlex per day, or a placebo (n=29), for 90 days. Subjects were assessed via the Six-Minute Walk Test and Stair Climb Test at baseline and after 90 days. Both TamaFlex groups saw an increase in average walking speed and improvements on Six-Minute Walk Test and Stair Climb Test scores compared to placebo, as well as reductions in pain and stiffness.

“The latest study on TamaFlex showed that it starts working in five days,” Anderson says. “This study, pending publication, explored how TamaFlex impacted subjects with mild to moderate joint pain from osteoarthritis. It showed improvements in pain, stiffness, physical activity, and stair climbing scores by day five.”

Other studies are demonstrating that turmeric can also be an effective joint health ingredient when incorporated into polyphenol blends. A recent open-label feasibility trial

 on Verdure Sciences’ (Noblesville, IN) branded curcumin/polyphenol blend Restoridyn examined the effects of the blend on blood inflammatory proteins and inflammation-associated RNA in 18 half-marathon runners for 29 days before, the day of, and the day after a race.

The participants received 1 g/day of Restoridyn for the first 26 days and 2 g/day on days 27 through 31. The subjects were also permitted to take an additional 1 g/day booster dose on days 1 through 26, but only on days when they ran more than 6 miles. Subjects were assessed for inflammation and soreness via testing for IL-10, IL-13, IL-4, TNF-alpha, and RNA biomarkers, among several others, on days 29 through 31.

The study found that Restoridyn altered several pathways associated with inflammation, B-cell activity, and muscle recovery. Restoridyn downregulated a type of long, non-coding RNA that is known to be involved in inflammation and COX-2 expression.

Kristen Marshall, digital marketing manager at Verdure Sciences, says the joint health market is beginning to diversify into more subcategories and specialized applications. Joint health brands are expanding into multiple functional arenas like exercise recovery and sports nutrition, joint comfort, pain and stiffness, inflammation, and overall healthy lifestyle.

“Joint health has evolved to include an ever-increasing array of applications, functions, and formats,” Marshall says. “We’re seeing many brands diversify their product offerings with innovative delivery forms like topicals, chocolates, functional beverages, and more.”

Research on other forms of turmeric is ongoing, and some of these studies show that an unconventional type of turmeric extract may offer substantial advantages. Brien Quirk, director of research and development for Draco Natural Products (San Jose, CA), says a water-soluble polysaccharide extract sourced from turmeric rhizomes was found to be very effective at relieving symptoms of osteoarthritis in a clinical trial

This study—a randomized, single-blind, placebo-controlled trial—examined the effects of NR-INF-02, a branded powdered curcumin rhizome product marketed as Turmacin by Natural Remedies Pvt. Ltd. (Bangalore, India), on pain and knee function in 120 subjects with knee osteoarthritis. Participants were randomly assigned to receive either 1) 400 mg of a placebo twice per day (n=30), or 2) 500 mg of Turmacin twice per day (n=30), 3) 750 mg of glucosamine sulfate twice per day (n=30), or 4) a combination of glucosamine sulfate and Turmacin twice per day (n=30), for 42 days. The subjects were assessed for pain via the VAS and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scales, and joint condition via the Clinical Global Impression Change (CGIC) scale, at baseline and after 21 and 42 days.

After 42 days, the subjects who received Turmacin showed a significant improvement in VAS, WOMAC, and CGIC scores and a significant decrease in the use of pain medication relative to placebo. The study authors concluded that Turmacin is a safe and effective option for relieving pain and improving knee function in osteoarthritis patients.

“Most of the turmeric extracts being sold on the market are standardized to a concentration of 95% curcumin and do not have water-soluble polysaccharides,” Quirk says. “Curcumin is very poorly absorbed, which explains why most turmeric extracts have not shown much benefit except in very large doses. Turmeric extracts that are rich in water-soluble polysaccharides have been ignored until now.”

Eggshell membrane ingredients are gaining popularity in joint health applications for their rich combination of joint-healthy compounds. Amanda Jepson, senior director of marketing and international sales for Biova LLC (Johnston, IA), says eggshell membrane is a source of multiple, naturally occurring compounds that promote joint health. These include ingredients like collagen, elastin, glucosamine, chondroitin, and several amino acids.

 on Biova’s branded BiovaFlex water-soluble egg membrane ingredient demonstrated robust results. The 12-week randomized, double-blind, placebo-controlled clinical trial examined the effects of a 450-mg daily dose of BiovaFlex (n = 44) on WOMAC scores and performance on the Six-Minute Walk Test relative to placebo (n = 44).

“The worst-performing subjects in the BiovaFlex group at baseline had the most significant improvement within five days,” Jepson says. “The BiovaFlex group also noted a reduction in joint stiffness within five days.”

New means of measuring the efficacy of ingredients are also lending momentum to the joint health space. Jacqueline Rizo, content coordinator for Stratum Nutrition (Carthage, MO), says that while joint health ingredients have typically been evaluated using pain and stiffness scales, recent innovations have made it possible to measure ingredient efficacy through objective biomarkers like CTX-II, the C-terminal telopeptide fragments of type II collagen.

“One of the significant developments related to NEM”—the company’s flagship eggshell membrane ingredient—“in recent months was the publication of research involved in the development of a clinical trial design for evaluating the effects of joint therapeutics on cartilage turnover,” Rizo says. “This clinical trial marked the first evidence suggesting CTX-II could be used to evaluate the chondroprotective efficacy of joint therapeutics in healthy individuals.”

 in question, sponsored by Stratum Nutrition’s parent company ESM Technologies (Carthage, MO), followed 60 healthy, postmenopausal women for 14 days. The women received either 500 mg of NEM per day (n=30), or a placebo (n=30), while doing step exercises (50-100 steps per leg) on alternating days. NEM administration resulted in faster recovery from exercise-induced joint pain and stiffness, as well as reduced discomfort, relative to placebo.

While the joint health benefits of methylsulfonylmethane (MSM) have been established for some time, recent clinical trials examining MSM in combination with other joint health ingredients have found that MSM has a synergistic effect.

Tim Hammond, vice president of sales and marketing for Bergstrom Nutrition (Vancouver, WA), says Bergstrom’s branded OptiMSM is ideal for new products because of its relative affordability, strong safety profile, and proven efficacy.

“Extensive research has shown that MSM decreases joint pain, improves stiffness and swelling, and increases the range of motion and physical function of individuals with osteoarthritis,” Hammond says. “OptiMSM’s likely mechanism stems from its ability to decrease pro-inflammatory cytokines, reduce oxidative damage, and supply a rich source of sulfur.”

One 2017 randomized, double-blind, placebo-controlled trial

 examined the performance of a glucosamine-chondroitin sulfate product both with and without MSM in relieving symptoms of osteoarthritis. The subjects, all of whom had either grade I or grade II osteoarthritis according to the Kellgren-Lawrence scale, received either 1) 1,500 mg of glucosamine and 1,200 mg of chondroitin sulfate (n=49), or 2) 1,500 mg of glucosamine, 1,200 mg of chondroitin sulfate, and 500 mg of MSM (n=50), or 3) a matching placebo (n=48) daily for three months. The subjects were assessed for joint pain on the WOMAC and VAS scales at baseline and after 4, 8, and 12 weeks. By the end of the study, the group that received the combination of glucosamine, chondroitin sulfate, and MSM exhibited the most significant improvements in WOMAC and VAS scores.

Various botanicals are showing promise as joint health supplements in clinical trials. Several of these products may present considerable advantages over legacy ingredients. Steve Fink, vice president of marketing for PLT Health Solutions (Morristown, NJ), says botanical ingredients like 

 take effect faster and require a lower dosage than some of the established ingredients in the market.

“If we look at the most commonly used natural solutions for mobility support, two things stand out: they require relatively large doses, and they require a long time to show efficacy,” Fink says.

 extracts and other botanicals have been found to take effect in as little as five days and to be effective with doses as low as 100 mg. PLT’s branded 

Dynagenix Muscle+Joint Formula, is a low-dose joint health ingredient that can be formulated in RTD products, powders, and more. One 2019 randomized, double-blind, placebo-controlled clinical trial examined the effects of Dynagenix Muscle+Joint Formula in 50 healthy, active men aged 25 to 40. In this unpublished study, subjects received 60 mg of 

 per day (n=25), or a matching placebo (n=25), for 10 days. Subjects underwent an eccentric exercise regimen, which involves muscles contracting and lengthening in quick succession, on day 7. The subjects were assessed for muscle and joint soreness via the VAS, knee range of motion, overall stiffness, and biomarkers of inflammation like IL-6 and cytokines at baseline and once daily on days 7 through 10. The subjects who received 

 experienced a reduction in joint soreness and a faster recovery of knee range of motion relative to the control group.

Another rich source of emerging joint health botanicals is the world of traditional Chinese medicine. David Liu, PhD, is the chief technology officer for Chenland Nutritionals (Irvine, CA). Liu says the reputation of certain joint health ingredients in traditional folk medicine systems like traditional Chinese medicine and Ayurveda is prompting researchers to take a closer look at these ingredients.

“With the development and utilization of omics and bioinformatics in these research fields, the scientific implication of herbal formulas has been elucidated, which has led to a better understanding of and acceptance by the western science community,” Liu explains. “Herbs like 

Dioscorea nipponica, Andrographis paniculata, 

have been clinically studied for their efficacies in relieving joint discomfort related to knee osteoarthritis.”

Chenland recently completed a six-month, open-label human clinical trial on its JointAlive ingredient, which contains extracts of 

 Bunge. Liu says that in this yet-to-be-published trial, JointAlive was 85% effective at reducing WOMAC scores. He says this trial also found that JointAlive begins to relieve joint discomfort in as little as two days.

Chenland is also actively pursuing a randomized, double-blind, placebo-controlled clinical trial

 on JointAlive in partnership with KGK Science (London, ON, Canada). This study, which is currently recruiting participants, will examine the efficacy of JointAlive in alleviating joint pain and improving knee function in an otherwise healthy population with mild to moderate knee osteoarthritis. Liu says the last subject will be enrolled in September 2021, and a final report on the clinical trial is expected by the end of this year.

Formulators are also looking toward botanical ingredients that are quite well known for applications in food. Steve Holtby, president and CEO of Soft Gel Technologies Inc. (Los Angeles, CA), says one emerging joint health ingredient is better known for its role in making beer.

“Hops, the ingredient used to add a touch of bitterness to most brews, has been studied because of its joint health properties,” Holtby explains. Soft Gel Technologies’ Perluxan softgels, derived from hops 

 “contain a unique botanical anti-inflammatory agent that has been clinically demonstrated to quickly relieve minor joint pain.”

Soft Gel Technologies exclusively markets Perluxan as a resin. Pharmachem Laboratories (Kearny, NJ), a division of Ashland (Wilmington, DE) that has performed extensive research

 on Perluxan, owns the trademark for Perluxan as a powder.

One randomized, double-blind, parallel-design trial

 on 19 subjects pitted Perluxan against ibuprofen. The subjects were randomly assigned to receive either 1) 400 mg of ibuprofen once per day, 2) a softgel containing 450 mg of the hops resin once per day, or 3) a 300-mg capsule containing a powdered form of the hops resin four times per day, for 14 days. Both hops formulations inhibited COX-2 as well as ibuprofen starting nine hours after the initial dose; however, the hops formulations did not inhibit COX-1, while ibuprofen did.

“It was interesting to note that the hops resin softgel was only administered once over a nine-hour period but was as effective as ibuprofen,” Holtby says. “The Perluxan softgel had a faster onset of action and gradually reduced pain-causing enzymes over the period of the study.”

Other botanical blends are also showing promise in joint health. Indena’s (Milan, Italy) branded Mitidol, a blend of ginger 

 underwent a pilot study that was published in 2020. This study

, a single-group pretest-posttest quasi-experimental trial, examined the effects of Mitidol on pain, inflammation, and knee function in 50 subjects aged 40 to 75 with knee osteoarthritis. All subjects received two 350-mg tablets of Mitidol daily for four weeks (n=50); there was no placebo group. The subjects were assessed for WOMAC and Tegner Lysholm Knee Scoring Scale scores at baseline and after 15 and 30 days. They were also evaluated for pain on the Visual Analogue Scale, quality of life via the 36-Item Short-Form Health Survey, and biomarkers of inflammation via C-reactive protein and erythrocyte sedimentation rate testing at baseline and after 30 days.

The subjects saw a significant decrease in VAS scores in the left and right knees after 10 and 11 days, respectively. WOMAC scores also decreased throughout the study, from a group average of 44 to 38. The group’s average Lysholm score increased from 65 at baseline to 73 after 30 days, indicating an improvement in knee function.

While several of the studies on botanicals for joint health have focused on aging older adults, this market is beginning to see interest from younger consumers—and Annie Eng, CEO of HP Ingredients (Bradenton, FL), says the next generation of joint health supplement users is already looking for clinically validated preventative maintenance products.

“The joint support market continues on a fast track of development as the Millennial generation, who are very active and health-conscious, begin to be proactive about joint care,” Eng says. “To ensure they and like-minded older adults have access to products that work to preserve joint structure and promote joint function, we are launching a new human clinical trial.”

This new study, led by Juan Hancke, PhD, is a randomized, double-blind, placebo-controlled clinical trial. The study will examine the effects of daily consumption of HP Ingredients’ branded 

product, ParActin, on knee function in knee osteoarthritis patients. The study will follow the subjects for one year. Earlier this year, ParActin received a natural product license from Health Canada.

The joint health space is seeing significant disruption and innovation. Emerging ingredients are gaining momentum as clinical trials prove their efficacy, carving out a place in the market next to more established competitors. As the joint health market continues to grow, products like turmeric, botanicals, and collagen will gain further traction. As this space grows more competitive, success in joint health will depend on convincing consumers that your ingredient stands on a strong foundation of science.

Sidebar: Hyaluronic Acid Normalizes Synovial Fluid

Michael Grenner, sales manager of food and nutrition raw materials, North America, at Bloomage Biotechnology USA (Hawthorne, NJ), says natural, non-GMO, and organic ingredients are growing in the joint-health space.

Grenner says hyaluronic acid is showing up in joint health formulations in combination with MSM, chondroitin, and other ingredients. Bloomage’s Haplex Plus contains sodium hyaluronate, the salt form of hyaluronic acid (HA). Studies have shown that HA can normalize synovial fluid

, and protect cartilage from denaturation

opened the door for a new joint-health contender. A 2021 randomized, double-blind, placebo-controlled trial found that a 350-mg daily dose of Gencor’s (Irvine, CA) Levagen, a branded palmitoylethanolamide (PEA) ingredient, reduced Visual Analogue Scale scores for joint pain in healthy adults aged 25 to 70. While the placebo group (n = 39) also saw a reduction in scores, that reduction lasted only 10 days before scores began to rise again, while the PEA group’s (n = 35) scores decreased over the entire course of the study.

“PEA demonstrated in the study its anti-inflammatory and analgesic properties, along with its ability to influence the endocannabinoid system,” says Maggie McNamara, marketing director for Gencor. “PEA downregulates multiple pro-inflammatory and nociceptive pathways and is known to inhibit glial cell activity.”

Sidebar: New Form of Chondroitin Improves Knee Function in OA Patients

has a long history of use in joint health, concerns around sourcing are leading to innovations in this ingredient. Xavier Berger, marketing manager for mobility and joint health at Gnosis by Lesaffre (Lille, France), says consumer concerns around animal welfare and cross-contamination have prompted formulators to source chondroitin from plants. Gnosis’s branded chondroitin product Mythocondro is one example of this trend.

“Mythocondro helps reduce the risk of osteoarthritis and joint degeneration,” Berger says. “Additional benefits include pain relief, anti-inflammatory activity, and increased articular function.”

 on Mythocondro found that a 600 mg/day dose reduced inflammation, WOMAC scores, and C-reactive protein levels in obese adults with moderate knee osteoarthritis after eight weeks.

Legacy ingredients are losing ground as emerging products gain validation. 

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